Laser-Scatter Measurement Instrument Having Carousel-Based Fluid Sample Arrangement

ABSTRACT

An instrument determines a concentration of bacteria in a plurality of fluid samples, and comprises a housing, a rotatable platform, a plurality of fluid containers, a light source, a sensor, and a motor. The rotatable platform is within the housing. The fluid containers are located on the rotatable platform. Each fluid container holds a corresponding one of the plurality of fluid samples, and has an input window and an output window. The light source provides an input beam for transmission into the input windows of the fluid containers and through the corresponding fluid samples. The input beam creates a forward-scatter signal associated with the concentration of bacteria. The motor rotates the rotatable platform so that the input beam sequentially passes through each fluid sample. A sensor within the housing detects the forward-scatter signal exiting from the output window associated with the fluid sample receiving the input beam.

RELATED APPLICATIONS

The present application claims priority to U.S. Provisional ApplicationSer. No. 62/107,931, filed Jan. 26, 2015, titled “Multi-SampleLaser-Scatter Measurement Instrument With Incubation Feature,” which isherein incorporated by reference in its entirety.

COPYRIGHT

A portion of the disclosure of this patent document may contain materialwhich is subject to copyright protection. The copyright owner has noobjection to the facsimile reproduction by anyone of the patentdisclosure, as it appears in the Patent and Trademark Office patentfiles or records, but otherwise reserves all copyright rights whatsoever

FIELD OF THE INVENTION

The present invention relates generally to the field of measurements ofbiological liquid samples. Specifically, the present invention relatesto systems and method for determining whether bacteria are present in aliquid sample and, if so, for determining the effect of chemoeffectorson the bacteria within the liquid sample.

BACKGROUND OF THE INVENTION

Many applications in the field of analytical research and clinicaltesting utilize methods for analyzing liquid samples. Among thosemethods are optical measurements that measure absorbance, turbidity,fluorescence/luminescence, and optical scattering measurements. Opticallaser scattering is one of the most sensitive methods, but itsimplementation can be very challenging, especially when analyzingbiological samples in which suspended particles are relativelytransparent in the medium.

One particle that often requires evaluation within a liquid is bacteria.The presence of bacteria is often checked with biological liquids, suchas urine, amniotic, pleural, peritoneal and spinal liquids. In a commonanalytical method, culturing of the bacteria can be time-consuming andinvolves the use of bacterial-growth plates placed within incubators.Normally, laboratory results take may take a day or several days todetermine whether the subject liquid is infected with bacteria and thetype of bacteria.

Quantification of bacteria, yeast, and other organisms in fluid can beuseful for medical diagnosis, drug development, industrial hygiene, foodsafety, and many other fields. Measurement of light scattering andabsorption in samples is a known method for approximating theconcentration of organisms. For example, techniques for detecting andcounting bacteria are generally described in U.S. Pat. Nos. 7,961,311and 8,339,601, both of which are commonly owned and are hereinincorporated by reference in their entireties.

Accordingly, there is a need for an improved systems and methods thatquickly determine whether bacteria is present in the fluid sample anddetermine the effect of chemoeffectors on a fluid sample. There is alsoa need for an improved systems and methods that more quickly determinethe type of bacteria after the presence of bacteria is determined.

SUMMARY OF THE INVENTION

The present invention is directed to an instrument for takingmeasurements of organism concentration in multiple fluid samples or in asingle fluid sample as a production tool for microbiology. Theinstrument may hold multiple, individually-loaded, independent fluidsamples and determine bacteria concentration of each sample via aforward-scattering signal. Or the instrument may hold a single fluidsample in multiple wells, which contain one or more differentchemoeffectors to act on the single fluid. Thus, the effects of achemoeffector (or concentrations of chemoeffectors) on the bacteriaconcentration in each fluid sample can be based on forward-scatteringsignals of the fluid sample over a period of time.

In one aspect, the instrument determines a concentration of bacteria ina plurality of fluid samples, and comprises a housing, a rotatableplatform, a plurality of fluid containers, a light source, a sensor, anda motor. The rotatable platform is within the housing. Each of theplurality of fluid containers is coupled to the rotatable platform. Eachof the fluid containers holds a corresponding one of the plurality offluid samples. Each of the fluid containers has an input window and anoutput window. The light source is within the housing and provides aninput beam for transmission into the input windows of the fluidcontainers and through the corresponding fluid samples. The input beamcreates a forward-scatter signal associated with the concentration ofbacteria. The motor rotates the rotatable platform so that the inputbeam sequentially passes through each of the plurality of fluid samples.At least one sensor within the housing detects the forward-scattersignal exiting from the output window associated with the fluid samplereceiving the input beam.

In yet a further aspect, the present invention is a method ofdetermining the concentration of bacteria in a plurality of fluidsamples. The method includes placing each of the fluid samples in acorresponding one of a plurality of fluid chambers located within acuvette. Each fluid chamber has a first window for receiving an inputbeam and a second window for transmitting a forward-scatter signalcaused by the input beam. The method further includes registering thecuvette on a rotatable platform associated with an optical measuringinstrument, incrementally rotating the rotatable platform so as tosequentially pass the input beam through each of the fluid samples, andin response to passing the input beam through each of the fluid samples,measuring a first forward-scatter signal for each of the fluid samples.

Alternatively, the present invention is an optical measuring instrumentfor determining a concentration of bacteria in fluid samples. Theinstrument comprises a housing, a door, a light source, and a rotatableplatform. The door is coupled to the housing. The door includes a doorplatform that extends inwardly into the housing when the door ispositioned in a closed state. The light source and a sensor measure anoptical signal from the fluid samples. The optical scatter signal isassociated with the concentration of bacteria. The rotatable platform iscoupled to the door platform. The rotatable platform receives one ormore cuvettes that hold the fluid samples. The rotatable platformsequentially moves each of the fluid samples into a testing position formeasurement by use of the light source and the sensor.

In yet another aspect, the present invention is an optical measuringinstrument for determining a concentration of bacteria in a plurality offluid samples. The instrument includes a cuvette, a first light source,a first sensor, a second light source, and a second sensor. The cuvettehas a plurality of optical chambers for receiving a respective one ofthe plurality of fluid samples. Each of the optical chambers is at leastpartially formed by an entry window for allowing transmission of aninput beam through the respective fluid sample and an exit window fortransmitting an optical signal caused by the bacteria within therespective fluid sample. A first group of the optical chambers containsa first group of the fluid samples. A second group of the opticalchambers contains a second group of the fluid samples. The first groupof the optical chambers is located on a first locus having a firstradius, and the second group of the optical chambers is located on asecond locus having a second radius. The first radius is different fromthe second radius. The first light source produces a first input beam.The first sensor receives a first optical signal that is responsive to abacterial concentration in the fluid sample and the first input beam.The first light source and the first sensor develop a first series ofoptical signals that are used for determining the concentration ofbacteria within each fluid sample of the first group of fluid samples.The second light source produces a second input beam. The second sensorreceives a second optical signal that is responsive to a bacterialconcentration in the fluid sample and the second input beam. The secondlight source and the second sensor develop a second series of opticalsignals that are used for determining the concentration of bacteriawithin each fluid sample of the second group of fluid samples.

In another aspect, the present invention is a cuvette for use in anoptical measuring instrument for determining a characteristic of aplurality of fluid samples. The cuvette includes a plurality of opticalchambers for receiving a respective one of the plurality of fluidsamples. Each of the optical chambers includes an entry window forallowing transmission of an input beam through the respective fluidsample and an exit window for transmitting an optical signal caused bythe respective fluid sample. A first group of the optical chambers islocated on a first locus having a first radius, while a second group ofthe optical chambers is located on a second locus having a secondradius. The first radius being different from the second radius.

Additional aspects of the invention will be apparent to those ofordinary skill in the art in view of the detailed description of variousembodiments, which is made with reference to the drawings, a briefdescription of which is provided below.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically illustrates an optical-measuring instrument that iscapable of testing fluid samples on a rotational platform.

FIG. 2 illustrates one detailed embodiment of the optical-measuringinstrument of FIG. 1 that uses the rotational platform.

FIG. 3 illustrates an underside perspective view of the door platform ofthe instrument of FIG. 2.

FIG. 4 illustrates a front perspective view of the instrument of FIG. 2with a portion of the housing removed and the door opened, such that therotational platform is in the loading position.

FIG. 5 illustrates a rear perspective view of the instrument of FIG. 2with a portion of the housing removed and the door and the rotationalplatform in the operational or closed position.

FIG. 6A illustrates a perspective view of a cuvette assembly that fitson the rotational platform of the instruments of FIGS. 1-5.

FIG. 6B illustrates an exploded perspective view of a single cuvette ofthe cuvette assembly of FIG. 6A.

FIG. 6C is a partial cross-sectional view of the main body of the singlecuvette of FIG. 6B.

FIG. 6D is a cross-sectional view through the main body of analternative cuvette assembly that fits on the rotational platform of theinstruments of FIGS. 1-5.

FIG. 6E is a cross-sectional view a bulk fluid-loading manifold that isused with the alternative cuvette of FIG. 6D.

FIG. 7 illustrates a system control diagram for the instruments of FIGS.1-5.

FIG. 8 is a cross-sectional view through the main body and two opposingfluid chambers of an alternative cuvette assembly that fits on therotational platform of the instruments of FIGS. 1-5.

While the invention is susceptible to various modifications andalternative forms, specific embodiments will be shown by way of examplein the drawings and will be described in detail herein. It should beunderstood, however, that the invention is not intended to be limited tothe particular forms disclosed. Rather, the invention is to cover allmodifications, equivalents, and alternatives falling within the spiritand scope of the invention as defined by the appended claims.

DETAILED DESCRIPTION

The drawings will herein be described in detail with the understandingthat the present disclosure is to be considered as an exemplification ofthe principles of the invention and is not intended to limit the broadaspect of the invention to the embodiments illustrated. For purposes ofthe present detailed description, the singular includes the plural andvice versa (unless specifically disclaimed); the words “and” and “or”shall be both conjunctive and disjunctive; the word “all” means “any andall”; the word “any” means “any and all”; and the word “including” means“including without limitation.”

FIG. 1 illustrates a general functional representation of an opticalmeasuring instrument 10 that has one or more light input beams that arefixed in position. Multiple sample chambers 12 (e.g., cuvettes) are heldby a rotatable platform 13 that moves each sample into the path of thelight input beam within the optical measuring instrument 10. The lightis developed by a light source, such as a laser 20 and may reflect off aturning mirror 21 before being transmitted through the fluid samplewithin the sample in the cuvette 12. A sensor 22 receives the opticalsignal (e.g., a forward-scatter signal), which is thenprocessed/analyzed to determine the presence and/or growth of bacteriaover a period of time. The optical measuring instrument 10 mayincorporate conductive heating and cooling, or radiant heating from anoptical or infrared source for control of the temperature of the fluidsamples, thereby providing proper incubation. These features aredescribed in detail below with reference to FIGS. 2-7.

FIG. 2 illustrates the instrument 10 that includes a housing 25 with adoor 27 that opens and closes on one end of the housing 25. The door 27includes a display device 28 that displays various pieces of informationabout the instrument 10. The display device 28 may provide informationregarding the test status (e.g., the current temperature within theinstrument 10 or the remaining minutes left in the test), the fluidsamples, and/or the test protocol being used for the fluid samples(e.g., time and temperature). Preferably, the display device 28 alsoincludes an associated touchscreen input (or a different set of inputbuttons can be provided) that allows a user to perform some of the basicfunctions of the instrument 10, such as a power on/off function, a dooropen/close function, a temperature increase/decrease function, etc.

The door 27 includes a door platform 29 that supports the rotatableplatform 13 for receiving the plurality of individual cuvettes 12 or acuvette assembly comprised of a plurality of cuvettes (e.g., the cuvetteassembly 90 shown in FIGS. 6A-6C). As such, the rotatable platform 13 isa carousel-like structure for transporting individual, discrete fluidsamples through a test protocol involving the repetitive transmission ofan input beam from the laser(s) 20 for measuring the forward scattersignal over a period of time to monitor a change in bacterialconcentration. To hold the fluid samples in a fixed orientation, therotatable platform 13 includes a plurality of registration posts 32 thatregister the cuvettes on the rotatable platform 13. Furthermore, therotatable platform 13 includes a plurality of openings that are alignedwith the cuvettes and permit transmission of the light input beamsassociated with the testing. A carousel-position sensor 33 is located onor within the door platform 29 for sensing the circumferential locationof the rotatable platform 13. The door 27 has seals and/or gasketsaround it so that the instrument 10 provides a light-tight enclosure toensure proper signal detection by the sensors 22.

FIG. 3 illustrates a lower view of the door platform 29. A stepper motor31 for rotating the rotatable platform 13 is positioned below andattached to the door platform 29. The stepper motor 31 provides thecarousel-like movement to the rotatable platform 13 through a shaft thatextends through the door platform 29. The door platform 29 also includesa plurality of openings 35 that serve different purposes. For example,some of the openings 35 b, 35 c, and 35 e are for receiving heat energyto maintain the rotatable platform 13 at a desirable temperature andencourage bacterial incubation. As discussed below with reference toFIG. 4, the heat energy is transmitted to the rotatable plate 13 from aplurality of lamps 44 located on the lower portion of the instrument 10within the housing 25. Another one of the openings 35 d is fortransmitting infrared radiation from the rotatable platform 13 to atemperature sensor located on the lower portion of the instrument 10.Two of the openings 35 a and 35 f are for transmitting to the sensors 22the forward scatter signal caused by the bacterial concentration withinthe fluid sample in response to the input beam laser 20 beingtransmitted into the fluid samples. The door platform 29 can includemore or less openings 35 depending on whether more or less functions arerequired from the bottom side of the door platform 29.

FIGS. 4 and 5 illustrate the arrangement of the internal components ofthe instrument 10. A first laser 20 a is designed to provide inputenergy for a first group of fluid samples, while the second laser 20 bis designed to provide input energy for a second group of fluid samples.The input energy from the first laser 20 a reflects from a first mirror21 a and is transmitted downwardly toward the first sensor 22 a. Theinput energy from the second laser 20 b reflects from a second mirror 21b and is transmitted downwardly toward the second sensor 22 b Thedetails of the transmission of energy through the fluid samples isdescribed in more detail below.

The lasers 20 and the sensors 22 are optically coupled in a fixedorientation via the mirrors 21. In one embodiment, the laser(s) 20 are avisible wavelength collimated laser diode. In another embodiment, thelaser(s) 20 deliver a laser beam from an optical fiber. In yet anotherembodiment, the laser(s) 20 include multiple wavelength sources fromcollimated laser diodes that are combined into a single co-boresightedbeam through one of several possible beam combining methods. In yet afurther example, the light source may be used that has an incoherentnarrow wavelength source such as an Argon gas incandescent lamp that istransmitted through one or more pinholes to provide a beam ofdirectionality. Each sensor 22 may include one or more the followingdevices—a camera, imager, calorimeter, thermopile, or solid-statedetector array.

FIGS. 4 and 5 also illustrate the thermal control system for theinstrument 10 that provides the incubation functionality. An infraredsensor 42 is located on the underside of the door platform 29 andmeasures the temperature of the rotatable platform 13 through theopening 35 d on the door platform 29. One or more lamp heaters 44 arelocated on the base structure of the instrument 10. The heaters 44create energy that is transmitted upwardly for warming the underside ofthe rotatable platform 13, thereby encouraging bacterial growth in thecuvettes. The energy is transmitted through the openings 35 b, 35 c, and35 e within the door platform 29 and is absorbed by the rotatableplatform 13, which may have a dark lower surface for absorbing theenergy.

A processor 50 is used to control the various aspects of the instrument10 as will be described in more detail below with regard to FIG. 7. Theinstrument 10 includes an external systems interface 70 that allows forthe instrument 10 to be connected to external systems. A port 80associated with the external systems interface 70 allows for the directconnection to a special use computer that is used to control theinstrument 10 and to receive information/data from the testing of thefluid samples. In addition to the display 28 located on the instrument10 (and preferably the input buttons and/or touchscreen on theinstrument 10), the instrument 10 communicates with an external device,such as a general purpose computer that would be coupled to a largerdisplay that displays the output of the tests in tabular or graphicalform. The instrument 10 can receive instructions from an external devicethat controls the operation of the instrument 10. The instrument 10 canalso transmit data (e.g., forward-scatter signal data, test-protocoldata, cuvette-assembly data derived from codes 62, as shown in FIG. 5,diagnostic data, etc.) from the port 30. The instrument 10 also includesan input power port (e.g., A/C power), which is then converted into a DCpower supply for use by the motors, laser, sensors, and displays, etc.

FIGS. 4 and 5 also illustrate a reader 60 adjacent to the rotatableplatform 13 for reading information from individual cuvettes or from acuvette assembly 90. Because a cuvette assembly 90 may be used fordifferent applications, the cuvette assembly 90 may include codes 62(e.g., via QR code or a barcode) or RFID tags to identify the type oftest supported by the particular cuvette assembly 90, as well as othermeasurement data to be taken. The instrument 10 preferably reads theRFID or barcode, and selects the software program stored in a memorydevice 55 (FIG. 7) to run the appropriate optical measurement tests onthe cuvette assembly 90. Accordingly, the cuvette assembly 90 preferablyincludes an identification label that includes one or more barcodesand/or QR codes that provide the necessary coded information for thecuvette assembly 90. Other codes can be used as well.

When bacteria is a particle being checked within the liquid sample, oneof the codes 62 may provide the protocol for the test (e.g., temperatureprofile over duration of test, frequency of the optical measurements,duration of test, etc.), and the processor 50 executes instructions fromthe memory 55 (FIG. 7) corresponding to the test protocol. Another oneof the codes may be associated with information on the patient(s) fromwhom the liquid samples were taken, which may include some level ofencryption to ensure that patient data is kept confidential. Anothercode may provide a quality-assurance check of the part number or theserial number for the cuvette assembly 90 to ensure that the cuvetteassembly 90 is an authentic and genuine part, such that impropercuvettes are not tested. The code for the quality-assurance check mayalso prevent a cuvette assembly 90 from being tested a second time(perhaps after some type of cleaning) if it is intended for only singleuse. Again, the instrument 10 includes the device(s) 60 (such as animage sensor, a barcode reader/sensor, or a QR-code reader/sensor) toread the codes 62 on the assembly 90. Alternatively, the codes 60 on thelabel can be scanned as the assemblies 90 are placed onto the rotatableplatform 13 (FIG. 5) such that the necessary information is obtainedprior to the door 27 being closed.

FIG. 5 also illustrates the cuvette assembly 90 in its operationalposition after being loaded onto the rotatable platform 13 when the door27 is opened. FIGS. 6A, 6B, and 6C illustrate the details of the cuvetteassembly 90. The cuvette assembly 90 includes a plurality offluid/optical chambers that are arranged in two circular (or arc-shaped)configurations. The outer circular configuration includes inner fluidchambers 92 positioned on a substantially circular locus. The cuvetteassembly 90 includes outer fluid chambers 94 positioned on asubstantially circular locus that has a larger radius than thesubstantially circular locus of the inner fluid chambers 92. As shown,the cuvette assembly 90 is comprised of seven individual cuvettes 91(only six are shown in FIG. 6A) that are preferably disposable and usedonly once. Alternatively, the cuvette assembly 90 can be comprised of aunitary annular-shaped structure, or two 180-degree cuvettes.

Each of the individual cuvettes 91 includes recesses 95 at its cornersthat allow the individual cuvettes 91 and, hence, the cuvette assembly90 to be registered in the proper location on the rotatable plate 13 bythe engagement of the recesses 95 with the registration posts 32 (seeFIG. 5). Other types of physical registration features or, perhaps,magnetic elements may be used to register the cuvette assembly 90 on therotatable plate 13. The registration of the cuvette assembly 90 on therotatable platform 13 ensures that the inner fluid chambers 92 and theouter fluid chambers 94 are aligned with the openings in theregistration platform 13. Accordingly, as the registration platform 13undergoes its carousel-like motion under the power of the motor 31, theinner radial openings in the registration platform 13 and the innerfluid chambers 92 are sequentially positioned over the opening 35 f inthe door platform 29 and the outer radial openings in the registrationplatform 13 and the outer fluid chambers 94 are sequentially positionedover the opening 35 a in the door platform 29. The openings 35 a and 35f (and the mirrors 21 and sensors 22) are geometrically arranged toensure that each time the motor 31 stops to align one outer fluidchamber 94 over the opening 35 a, there is a generally opposing innerfluid chamber 92 aligned over the opening 35 f. However, because thereare more outer fluid chambers 94 than inner fluid chambers 92, one360-degree cycle of testing the fluid chambers 92, 94 around the cuvetteassembly 90 requires less testing (i.e., less sequential inputs from thelaser 20 a) of the inner fluid chambers 92 than the outer fluid chambers94. In other words, in the illustrated embodiment, the laser 20 b isoperational for forty-two tests of the forty-two outer fluid chambers 94during a 360-degree rotation of the rotatable platform 13, while thelaser 20 a is operational for only thirty-five tests of the thirty-fiveinner fluid chambers 92 during the same 360-degree rotation of therotatable platform 13.

As shown best in FIGS. 6B and 6C, each of the fluid chambers 92 and 94is bound at its upper and lower ends by an upper window 93 a and a lowerwindow 93 b, respectively. The upper window 93 a is formed on a topcover 96 that snaps onto a main body 97 of the cuvette 91. The upperwindow 93 a extends downwardly into the fluid chamber such that it is incontact with the fluid sample within the fluid chamber. The lower window93 b is a thin layer (preferably made of optical grade plastic) that isattached to the lower portion of the main body 97. The lower window 93 bforms a bottom of the fluid chamber.

Each of the fluid chambers 92 and 94 includes multiple portions. Thesmaller portion 98 connects into a larger portion 99. In use, each ofthe fluid chambers 92 and 94 is filled with the fluid sample before thetop cover 96 has been attached. Each of the fluid chambers 92 and 94receives a known amount of fluid, such that, when the top cover 96 isattached to the main body 97, the upper window 93 a extends downwardlyinto the fluid chamber, contacts the fluid, and displaces the fluid in amanner that allows the fluid to move upwardly along the surface definingthe smaller portion 98. Accordingly, the small portion 98 of each fluidchamber provides a spatial volume to accommodate the fluid displacementthat occurs when the top cover 96 moves downwardly and the top window 93a engages the fluid. During operation, the input beam enters the largerportion 99, which acts as an optical chamber, and the resultantforward-scatter signal exits from the lower window 93 b. Each fluidsample may undergo some type of filtering within the cuvette assembly 90(not shown) and/or outside the cuvette assembly 90 such that unwantedparticles are substantially filtered, leaving only (or predominantlyonly) the bacteria.

To sequentially move the cuvette assembly 90 on the rotatable platform13 in the operational mode, the motor 31 incrementally advances in acarousel-like fashion to align one outer fluid chamber 94 below themirror 21 b and above the sensor 22 b so as to receive input energy fromthe laser 20 b that causes the forward-scatter signal. And when one ofthe outer fluid chambers 94 is so aligned, a corresponding one of theinner fluid chambers 92 on a generally opposing side of the cuvette 90is aligned below the mirror 21 a and above the sensor 22 a so as toreceive input energy from the other laser 20 a. As such, two opposingfluid samples on the cuvette assembly 90 can be simultaneously tested orsequentially tested (with little or no time between sequentially firingsof the lasers 20 a and 20 b), and monitored via the correspondingforward-scatter signals. The circumferential spacing between adjacentouter fluid chambers 94 and inner fluid chambers 92 is selected to be aknown circumferential distance that corresponds to predetermined numberof rotational increments of the motor 31. In other words, as an example,if four increments of rotational movement of the motor 31 is known tocreate a 2-cm arc distance at a radius measured from the shaft of themotor 31 to the center points of the outer fluid chambers 94, then thecenter points for two adjacent outer fluid chambers 94 can be set at 2cm in the design of the cuvette 90, knowing that four increments ofoperation of the motor 31 is needed to transition between adjacent outerfluid chambers 94.

The carousel-position sensor 33 (FIG. 3) located within the doorplatform 29 is used to sense the location of the rotatable platform 13and, hence, the cuvette assembly 90. The carousel position sensor 33 mayinclude an encoder that is used to register the position of each of theinner and outer fluid chambers 92, 94 relative to the input beams of thelasers 20. Alternatively, the laser(s) 20 and sensor(s) 22 can be usedfor cuvette-orientation purposes if some of the openings within therotatable platform 13 remain open (i.e., not covered by a cuvette) andsized in a way to provide a certain signal for the sensor(s) 22 toreceive. As the rotatable platform 13 undergoes the carousel-like motionto begin the operational mode and register the first fluid chamberrequiring testing, the lasers 20 and corresponding sensors 22 canidentify the circumferential location of the first fluid chamber byidentifying these unused and differently sized openings within therotatable platform 13 as it rotates. The processor 50, upon receivingthe signal output from the sensors 22, then selectively controls themotor 31 to place the first fluid chamber to be tested in theappropriate circumferential position under one of the input beamsreflected from the mirror 21 a or 21 b.

FIGS. 6D illustrates an alternative embodiment of a cuvette 130, whichcould be annular-shaped like the cuvette assembly 90 or arc-shaped likethe individual cuvette 91 in FIGS. 6A-6C. The cuvette 130 is shown incross-section through the main body 131 in the region of a single innerfluid chamber 132 and a single outer fluid chamber 134, although thecuvettes 130 would have numerous inner fluid chambers 132 and outerfluid chambers 134 (e.g., forty-two outer fluid chambers 134 andthirty-five inner fluid chambers 132). An upper window 133 a is attachedto the main body 131 in the region of the outer fluid chamber 134, whilean upper window 133 b is attached to the main body 131 in the region ofthe inner fluid chamber 132. Each of the upper entry windows 133 a and133 b may be annular shaped (or arc-shaped) such that it fits entirely(or partially) around the cuvette 130 (e.g., the window 133 a is aunitary piece of optical grade plastic that covers all of the outerfluid chambers 134 and the window 133 b is a separate unitary piece ofoptical grade plastic with a slightly smaller radius that covers all ofthe inner fluid chambers 132). A lower exit window 135 is also attachedto the main body 131 and, as illustrated, is a unitary piece of opticalgrade plastic that covers the bottom of all of the inner fluid chambers132 and the outer fluid chambers 134. Individual entry windows 133 andexit windows 135 can be used as well. The cuvette 130 is shown restingon the rotatable platform 13, which has openings aligned with all of theinner fluid chambers 132 and the outer fluid chambers 134, as notedabove with respect to FIGS. 6A-6C.

Each of the inner fluid chambers 132 and the outer fluid chambers 134includes a main volume 136 for holding the fluid sample during the testsin which the input beam from the laser 20 reflects off the mirror 21,transmits through the fluid sample, and creates a forward scatter signalthat is received by the sensor 22. Directly adjacent to the main volume136 is a fluid input port 137 extending upwardly above the overallheight of the main volume 136 to ensure that sample fluid that isreceived within each of the fluid chambers will engage the lower surfaceof the upper window 133. Accordingly, by having the fluid input port 137located above (relative to the gravitational gradient) the upper window133, the fluid sample should completely fill the main volume 136 undergravity without bubbles, which can be problematic for operation. Duringoperation, the input beam enters the main volume 136, which acts as anoptical chamber, and the resultant forward-scatter signal associatedwith the bacterial concentration (or other particles in the fluid) exitsfrom the lower window 135 and passes through an opening in the rotatabletable 13. The cuvette 130 may also include a cap 140 having resilientlower bosses that fit within each of the fluid input ports 137 of theinner fluid chambers 132 and the outer fluid chambers 134 to seal thecuvette 130 after its chambers have been filled. The cap 140 can beannular-shaped or arc-shaped, depending on the overall shape of thecuvette 130.

FIG. 6E illustrates one example of a fluid-input manifold 150 that canbe used to simultaneously fill all of the inner fluid chambers 132 andthe outer fluid chambers 134 with a single type of fluid sample. Thefluid-input manifold 150 includes a series of inner fluid channels 152and a series of outer fluid channels 154. The inner fluid channels 152are designed to fit within the fluid input ports 137 of the inner fluidchambers 132. The outer fluid channels 154 are designed to fit withinthe fluid input ports 137 associated with the outer fluid chambers 134.After the fluid input manifold 150 has been installed onto the cuvette130, a known amount of fluid that is needed to collectively fill all ofthe inner fluid chambers 132 and outer fluid chambers 134 in the cuvette130 can be filled into the upper portion of the manifold 150, such thatthe sample fluid simultaneously fills each of the inner fluid chambers132 and the outer fluid chambers 134 within the cuvette 130. To ensurethat the fluid amount does not rise to the top of each of the fluidinput ports 137, the amount of material that is used to create each ofthe inner fluid channels 152 and 154 (which extend into the fluid inputports 137) can be tailored so as to create a known non-fluid volumewithin each fluid entry port 137. After the removal of the manifold 150from the cuvette 130 after the filling process is complete, there isadded volume created within each fluid entry port 137 to receive thesample fluid, resulting in the upper surface of the sample fluid withineach inner input port 137 falling below the upper surface of the mainbody 131. The cap 140 can then be placed over each of the fluid inputports 137, as described above with reference to FIG. 6D. The manifold150 may have a closed top with a needle-free swabable port valve forreceiving a known volume of fluid. In this arrangement, the inner fluidchambers 132 and the outer fluid chambers 134 of the cuvette 130 can beindividually loaded (e.g., when numerous different fluid samplestested), or they can be “bulk” loaded with a single fluid sample by useof the manifold 150.

FIG. 7 illustrates one embodiment for a control system that is locatedwithin the instrument 10. The instrument 10 includes one or more printedcircuit boards that include at least one processor 50 (and possiblyseveral processors) and at least one memory device 55. The processor 50communicates with the memory device 55, which includes various programsto operate the motor(s), the laser, the sensors, the heating system, thebasic operational functionality, diagnostics, etc. The processor 50 isin communication with the functional components of the instrument 10,such as (1) the optical sensors 22 a and 22 b that sense theforward-scatter signals (or other optical signals, such as fluorescencesignals), (2) the lasers 20 or other light source that creates the lightbeam is transmitted into the cuvettes, (3) temperature sensor(s) 42 thatdetermines the temperature of the rotatable plate 13 or within thehousing 25 (or associated with the surface of the cuvette), (4) theheating system 44, which includes the heater lamps and/or the otherheating elements, (5) the motors 31 used for rotating the platform 13,(6) the display(s) 28 on the front of door 27 of the instrument 10, (7)any user input devices 66 (mechanical buttons or touchscreens), (8) anaudio alarm 68 to alert the operator of the instrument 10 to aparticular condition or event (e.g., to indicate that one or moresamples have reached a certain testing condition, such as a highbacterial concentration, a certain slope in a bacterial-growth curve hasbeen achieved, or a certain forward-scatter signal exceeds a certainvalue), (9) the carousel-position sensor 33 on the door platform 29, and(10) the cuvette reader 60 for reading codes that provide informationregarding the cuvettes, the testing protocol, etc.

The processor 50 is also communicating with an external systemsinterface 70, such as interface module, associated with the output port80 on the instrument 10. The primary functions of the processor(s) 50within the instrument 10 are (i) to maintain the enclosure within theinstrument 10 at the appropriate temperature profile (temperature versustime) by use of the temperature sensors 42 and heating system 44, (ii)to sequentially actuate the lasers 20 a and 20 b so as to provide thenecessary input beam into the samples within the cuvette assembly 90,(iii) to controllably rotate the platform 13 via the motor 31 and thecarousel-position sensor 33 to ensure proper alignment of the input beamand the chamber containing the fluid sample, (iv) to receive andstore/transmit the data in the memory device 55 associated with theoptical (e.g., forward-scatter) signals from the sensors 22 a and 22 b,and (v) possibly, to analyze the forward-scatter signals to determinethe bacterial concentration. Alternatively, the control system orcomputer module that controls the instrument 10 could be partiallylocated outside the instrument 10. For example, a first processor may belocated within the instrument 10 for operating the laser, motors, andheating system, while a second processor outside the instrument 10handles the data processing/analysis for the forward-scatter signalsreceived by the sensors 22 a and 22 b to determine bacterialconcentration. The test results (e.g., bacterial concentrationindication) and data from the instrument 10 can be reported on theinstrument display 28 and/or transmitted by USB, Ethernet, wifi,Bluetooth, or other communication links from the external systemsinterface 70 within the instrument 10 to external systems that conductfurther analysis, reporting, archiving, or aggregation with other datawithin a network. In one preferred embodiment, a central databasereceives test results and data from a plurality of remotely locatedinstruments 10 such that the test data and results (anonymousdata/results) can be used to determine trends using analytics, which canthen be used to derive better and more robust operational programs forthe instrument 10 (e.g., to decrease time per test, or decrease theenergy of the tests by used lower incubation temperatures).

The instrument 10 in FIGS. 1-7 uses laser-scattering technology toquantify bacteria growth in fluid sample sizes that are smaller than 0.5ml, and preferably about 0.1 ml. Each of the fluid chambers 132, 134provides enough vertical height (e.g., about 10 mm to 12 mm) to causethe desired interaction of the laser beam with the bacteria to producethe forward scatter signal. The upper entry windows preferably are morethan twice the diameter of the input beam, which is usually less than 1mm, and preferably between about 0.5 mm and 0.75 mm. Hence, the upperwindows have a diameter in the range from about 2 mm to 2.5 mm. Thedivergence of the input beam as it passes through the fluid sample iswithin about 8° as measured from the central axis, such that the exitwindows typically have a diameter in the range from about 4 mm to 5 mm.The volume and shape of the fluid chambers is also configured tominimize bubbles. In particular, the instrument 10 transmits a beam fromeach laser 20 a, 20 b through a fluid sample, and measures the scattersignal at the sensors 22 a, 22 b caused by the bacteria in the fluidsample, preferably through a forward-scattering measurement technique.The on-board incubation through the heating system 44 and temperaturesensor 42 provides for fluid sample temperatures ranging from roomtemperature up to 42° C. (or higher). The instrument 10 permits for arange of optical measurement intervals over a period of time (e.g., 1-6hours) to determine the growth and concentration of the bacteria withinthe liquid samples during incubation. The optical measuring instrument10 can detect and count bacteria by various techniques that aregenerally described in U.S. Pat. Nos. 7,961,311 and 8,339,601, both ofwhich are commonly owned and are herein incorporated by reference intheir entireties.

Due to the incubation feature within the instrument 10, the necessaryenvironment around the cuvette assemblies 90 can be controlled topromote the growth of the bacteria, such that subsequent opticalmeasurements taken by the combination of the lasers 20 a and 20 b andthe sensor 22 a and 22 b results in a stronger forward-scatter signalindicative of increased bacterial concentration. The instrument 10includes internal programming that (i) controls the environment aroundthe fluid sample and (ii) dictates the times and/or times-intervalsbetween optical measurements to determine whether the bacteria has grownand, if so, how much the concentration of bacteria has increased. Thereal-time output from the instrument 10 can be seen on a separatedisplay coupled to the port 80.

In one mode of operation of the instrument 10, the fluid samples in thecuvette assembly 90 (or each individual cuvette 91) is from a singlesample (e.g., from a single patient) Each of the fluid chambers 92 and94 could be pre-loaded with a certain chemoeffector (different types anddifferent amounts of each type) including a drug, antimicrobial agent,nutrient, chemical tag or colorant. Each optical chamber is thensequentially measured with one or more optical beam lines, or by movingthe fluid samples through the input beam lines below the mirrors 22. Ifeach individual optical chamber includes a different chemoeffector(e.g., different dosage of an antibiotic), then the effect of theseparate chemoeffector can be monitored over time for a single fluidsample. Thus, the instrument 10 in can be used to determine the effectsof a chemoeffector (a drug, antimicrobial agent, nutrient, chemical tagor colorant) on a single sample if the cuvette assembly 90 (orindividual cuvette 91) is loaded with a sample from a single patient,but the chambers includes different chemoeffectors. In this scenario,the instrument 10 may test a single patient's sample against multiplechemoffectors. As such, the measurement instrument 10 in conjunctionwith the cuvette assembly 90 can be used to determine the effects of achemoeffector (e.g., a drug, antimicrobial agent, nutrient, chemical tagor colorant) on a single sample if the cuvette (such as cuvettesassembly 90 or individual cuvettes 91) is loaded with a single sample(e.g., from a single patient), but the optical chambers includesdifferent chemoeffectors (or each the seven cuvettes 91 in the cuvetteassembly 90 is designed to test a single chemoeffector eleven times viathe eleven fluid chambers 92, 94 for accuracy/repeatability). The codes62 on the label on the cuvettes 91 of the assembly 90 may identify whichchemoeffector is being tested within the respective cuvette 91.

FIG. 8 illustrates a different rotatable cuvette assembly 190 for theinstrument 10 in which a single sample is constituted from one ormultiple liquids and/or dry materials that are combined and mixed. Thecuvette assembly 190 includes a port 196 for addition of thesematerials, and a central chamber 194 for mixing of materials. Filters197 may be used to minimize the particles that are transferred into thecentral mixing chamber 194. The rotatable cuvette assembly 190 includesan arrangement of a plurality of measurement chambers 192 (e.g.,cuvettes) configured around the central chamber 194 with passages orchannels 195 defined by walls 198 for communicating the liquid from thecentral mixing chamber 190 to the peripheral measurement chambers 192.The cuvette 190 may have several peripheral measurement chambers 192(e.g., thirty or forty) arranged around the central chamber 194 in waysto permit the use of both lasers 20 a and 20 b and sensors 22 a and 22b. The passages 195 may be configured above the intended fill level ofthe central mixing chamber 194 and could be sloped such that rotation ofthe assembly 190 would centrifugally force liquid up to the passages 195and then into the peripheral measurement chambers 192. Alternatively oradditionally, valves or seals within the passages 195 could beconfigured to preclude flow to the measurement chambers untilsatisfactory mixing is completed. The port 196 may be coupled to aneedle-free swabble input valve 199 to eliminate or inhibit dripping ofthe sample fluid as the cuvette assembly 190 is being loaded.

The central mixing chamber 194 and the peripheral measurement chambers192 can be made of a disposable plastic material, such that they areused for only a single sample. Similarly, the walls 195 defining thepassages 198 can be made of a similar plastic material. In oneembodiment, a single disposable unit would include a spider-likeconfiguration having the central chamber, the passages/channels, and theperipheral measurement chambers, all of which snap into (or fit within)corresponding structures (e.g., registration posts 32) of the rotatableplatform 13 of the instrument 10 that provides for the rotationalmovement and optical sensing.

In an additional embodiment, each of the peripheral measurement chambers192 could be pre-loaded with a chemoeffector including a drug,antimicrobial agent, nutrient, chemical tag or colorant. The singlefluid sample can be constituted in the central chamber 194, mixed byrotation of the chamber (perhaps assisted by vanes or paddles in thecentral chamber), and then centrifugally distributed to the peripheralmeasurement chambers 192 by spinning of the assembly 190. Eachperipheral measurement chamber 192 is then sequentially measured byrotation of the assembly 190 to move the individual measurement chambers190 into position with one or more optical beam lines defined betweenwith the laser 20 (or mirror 21) and the sensor 22. Alternatively, adifferent instrument may move the beamlines around the sample assembly190. If each individual measurement chamber includes a differentchemoeffector (e.g., different dosage of an antibiotic), then the effectof the separate chemoeffector can be monitored over time.

To the extent the fluid samples require mixing or agitation, therotatable platform 13 may be equipped with a vibration-producingmechanism to help agitate the samples in the cuvette assembly 90. Forexample, the motor 31 can be operated in mode whereby it repetitivelymoves the cuvette assembly 90 back-and-forth to provide the necessarymixing.

In yet another embodiment of the instrument 10, the light source 20 andthe sensor 22 are fixed, and the multiple sample chambers are fixed aswell. However, optical elements such as mirrors or prisms onelectro-mechanical actuators are used to move the light beam frommeasurement chamber to measurement chamber within each sample. Hence,the electro-mechanical actuators and possibly motors are used to movethe light beam, while the light source, the sensor(s), and the multiplesample chambers are fixed. A single light beam source can also be splitinto multiple input beams used with the mirrors 22 a and 22 b.

Regarding the measurement of bacteria, the instrument 10 preferablymeasures bacteria and other organisms generally in the range for 0.1 to10 microns with a measurement repeatability of 10%. The instrument 10can measure a low concentration of 1×10⁴ cfu/ml (based on E-coli infiltered saline) and deliver continuous measurements showing growthbeyond 1×10⁹ cfu/ml. The instrument 10 can be loaded with factory-setcalibration factors for approximate quantification of common organisms.Further, the user can load custom calibration factors with specific testprotocols for use with less common organisms or processes.

Considering that the particles in the fluid (especially bacteria) may bein motion, it is possible that large clusters may affect theforward-scatter signal on any given test sample. Accordingly, in onepreferred embodiment, multiple consecutive test data points for eachfluid sample are averaged to avoid having a single forward-scattersignal with a large cluster of particles or a single forward-scattersignal corresponding to only a few particles affect the overall testresults. In one example, five consecutive forward-scatter signal testdata points are averaged under a rolling-average method to develop asingle average signal. Thus, as a new data point is taken for eachsample, it is used with the previous four data points to develop a newaverage. More or less data points than five can be used for this rollingaverage. Further, the computation methodology may use various algorithmsto remove the high and low signals (or certain ultra-high or ultra-lowsignals) before taking the average. Or, the computation methodology canbe as simple as choosing the mathematical median of a data set.Ultimately, the forward-scatter signals from the instrument 10 willproduce a bacterial-growth curve having a certain slope over a period oftime at an appropriate incubation temperature.

Generally, growth curves are numerically filtered and analyzed fordetermination of initial concentration, growth percentage for apredefined period of time, and changes in the growth rate. Determinationof bacterial absence or bacterial presence above a predefined thresholdis based on a combination of those parameters with thresholds that arecharacteristic for bacterial growth and salts crystallization/dissolvingkinetics. In one basic example, if the slope is above a predeterminedvalue, the patient's sample is infected. Alternatively, it could be thatthe slope that indicates the presence of an infection may be differentfor different periods of time (e.g., Slope_(infection)>X within T=0 to30 minutes; Slope_(infection)>1.5X within T=30 to 60 minutes; etc.)

Particles with a refractive index different from the surrounding mediumwill scatter light, and the resultant scattering intensity/angulardistribution depends on the particle size, refractive index and shape.In situations in which the input light is scattered more than one timebefore exiting the sample (known as multiple scattering), the scatteringalso depends on the concentration of particles. Typically, bacteria havea refractive index close to that of water, indicating they arerelatively transparent and scatter a small fraction of the incidentbeam, predominantly in the forward direction. With the optical designwithin the instrument 10, it is possible to look at scattering anglesdown to about 2° without having the incident input beam or other noisesignals (e.g., the scattering from the cuvette windows) interfere withlight scattered by bacteria. By simultaneous measurement of the forwardscattering and optical density, measurements could be extended down to10⁻⁵, allowing accurate measurement of concentrations as low as 10³CFU/mL.

Optical density measurements are intended to determine sampleconcentrations that are not accurate, as the size of the scatteringparticles greatly affects the resulting optical density. A similaroptical density is obtained for samples with a few large size bacteriain comparison with a higher concentration of small size bacterialsamples. Moreover, additional calibration of the optical density toconcentration does not render more accurate results, since the sizechanges during the bacterial growth process.

It is also possible to use the instrument 10 to measure the number ofbacteria within the fluid sample. By use of the Mie scattering model forspherical particles and the T-matrix method of light scattering,combined with Monte-Carlo ray tracing calculation that takes intoaccount multiple scattering, it is possible to evaluate the number ofbacteria and their size from the measurement of the optical density andthe scattered light angular distribution.

The results are nearly independent of the specific particle shape andloosely depend on the size dispersion of bacteria, resulting in a smallconstant shift of the mean size. Thus, both bacterial concentration andsize are evaluated from the measured parameters by a first principlemodel without any free parameters, except the bacteria refractive index,that is measured by calibration for each of the bacteria species. Inshort, the instrument 10 can be used to detect forward scatter signalscorresponding to scattering intensity and angular distribution (e.g.,for angles less than 5°, such as angles down to about 2°) and also theoptical density of the fluid samples, which can then be evaluated todetermine the number of bacteria and their sizes (and changes to thenumber of bacteria and to their sizes over a period of time).

The system and method associated with FIGS. 1-8 have various uses andapplications. For example, in the area of research, it can be used for(i) microbial concentration and grow analyses, (ii) quantification ofantimicrobial, antibiotics, and environmental effects, and (iii)antibiotic drug development and clinical trial enrollment. In the areaof hygiene and safety, it can be used for (iv) antimicrobial andantibiotics quality assurance testing, (v) process and potable watertesting, and (vi) surface, wipe, and swab microbial testing. In the areaof clinical microbiology for humans and animals, it can be used for(vii) rapid detection and quantification of infection, (viii) rapidantibiotic susceptibility testing (AST), (ix) drug-testing andmeasurement, and (x) antibiotic sensitivity testing for quality control.

The present invention associated with FIGS. 1-8 also contemplates theidentification (or partial identification) of the type of bacteria thatis present in fluid sample. For example, if a certain type of fluid isknown to have a limited number of types of bacteria, one type ofbacteria may be known to grow at a fast rate at a certain incubationtemperature relative to the other bacteria, leading to a higher slope onthe growth curves. One type of bacteria may be known to grow at a slowerrate at a certain incubation temperature relative to the other bacteria,leading to a lower slope on the growth curves. Or a group of bacteriamay be known to have certain growth curves, leading to the partialidentification by eliminating the other types of bacteria that may bepossibly present in the fluid sample. Using multiple instruments 10 withthe same set of fluid samples but at different incubation temperatures(e.g., the same samples in three instruments 10 at 38° C., 40° C., and42° C.) can result in different bacterial-growth curves, which identifyone type of bacteria relative another (or at least a species ofbacteria). Further, if one bacteria (or a species of bacteria) are knownto die above a certain temperature, then after the samples have beentested, the instrument 10 can ramp-up the temperature to see if thegrowth curve flattens for any sample, indicating that the sample may beinfected by the bacteria that is known to die above the operatingtemperature.

In a further example, complex UTI cases in humans are known to have bothGram Positive bacteria and Gram Negative bacteria. Crystal Violet is adye that adheres to the rough surface of Gram Positive bacteria and, inthe process, causes the pores on the surface to become “clogged” so asto kill the Gram Positive bacteria. Therefore, inclusion of CrystalViolet in one or more fluid chambers 92, 94 of the cuvette assembly 90while other chambers in the cuvette assembly 90 lack it permitsidentification of the UTI infection type. If the bacteria growth curvecontinues similarly in both chambers, then the patient's sample islikely infected by only a Gram Negative bacteria. On the other hand, ifthe bacteria growth curve in the chamber having Crystal Violet has asubstantially smaller slope, then the infection likely includes a GramPositive bacteria. As such, at least a partial identification of thebacteria has been achieved. In this case, the chemoeffector is an inertchemistry (Crystal Violet) that impacts the growth behavior of theorganisms, and by comparison to a control, some identificationinformation for the bacteria can be obtained.

Each of these embodiments and obvious variations thereof is contemplatedas falling within the spirit and scope of the claimed invention, whichis set forth in the following claims. Moreover, the present conceptsexpressly include any and all combinations and subcombinations of thepreceding elements and aspects.

1. (canceled) 2-9. (canceled)
 10. A method of determining theconcentration of bacteria in a plurality of fluid samples, comprising:placing each of the fluid samples in a corresponding one of a pluralityof fluid chambers located within a cuvette, each fluid chamber having afirst window for receiving an input beam and a second window fortransmitting a forward-scatter signal caused by the input beam;registering the cuvette on a rotatable platform associated with anoptical measuring instrument; incrementally rotating the rotatableplatform so as to sequentially pass the input beam through each of thefluid samples; and in response to passing the input beam through each ofthe fluid samples, measuring a first forward-scatter signal for each ofthe fluid samples.
 11. The method of claim 10, further including:incubating the fluid samples in the optical measuring instrument beforeand after measuring the first forward-scatter signal; and after a periodof time, sequentially passing the input beam through each of the fluidsamples and measuring a second forward-scatter signal for each of thefluid samples, a difference between the first forward-scatter signal andthe second forward-scatter signal for each of the fluid samples beingindicative of a change in the concentration of bacteria.
 12. The methodof claim 11, further including determining that at least one fluidsample includes a certain concentration of bacteria in response to thedifference between the first forward-scatter signal and the secondforward-scatter signal.
 13. The method of claim 10, wherein theplurality of fluid containers include at least one of (i) a singlechemoeffector at different concentrations and (ii) differentchemoeffectors,the plurality of fluid samples being derived from thesame fluid sample source, the method further includes determining theeffects of the different concentration of a chemoeffector or thedifferent chemoeffectors based, in part, on the measuring of the firstforward-scatter signal. 14-18. (canceled) 19-23. (canceled) 24-26.(canceled)
 27. An optical measuring instrument for anti-microbialsusceptibility testing on a fluid sample containing bacteria,comprising: a housing; a rotatable platform within the housing; a singlecuvette containing a plurality of fluid containers coupled to therotatable platform and including and including an input window and anoutput window, the fluid containers containing at least oneantimicrobial agent, each of the individual fluid containers receiving aportion of the fluid sample such that the fluid sample can be mixed withthe at least one antimicrobial agent; a light source within the housingfor providing an input beam for transmission into the input windows ofthe fluid containers, wherein the input window and the output window arevertically arranged with the fluid sample located therebetween, a motorfor rotating the rotatable platform so that the input beam sequentiallypasses through each of the plurality of fluid samples; and at least onesensor within the housing below the rotatable platform and cuvette, theat least one sensor for detecting a forward-scatter signal exiting fromthe output window of the corresponding fluid container that receives theinput beam, the forward-scatter signals for each of the plurality offluid containers being measured over a period of time to determine thesusceptibility of the bacteria in the fluid sample to the correspondinganti-microbial agent within the fluid container.
 28. The opticalmeasuring instrument of claim 27, further comprising a first mirrormounted to reflect the input beam in a vertical direction through theinput window, the input beam creating the forward-scatter signalassociated with the concentration of bacteria.
 29. The optical measuringinstrument of claim 27, further comprising a heating system within thehousing to maintain the fluid samples at a desired temperature.
 30. Theoptical measuring instrument of claim 29, wherein the heating systemincludes a plurality of heat lamps that provide energy to a bottomsurface of the rotatable platform, a top surface of the rotatableplatform receiving the plurality of fluid containers.
 31. The opticalmeasuring instrument of claim 27, wherein the rotatable platform has aplurality of openings that are aligned with the output windows of thesingle cuvette.
 32. The optical measuring instrument of claim 27,further comprising a second light source within the housing forproviding a second input beam for transmission into the input windows ofthe fluid containers, the second input beam creating a forward-scattersignal associated with the concentration of bacteria, the light sourcefor measuring the susceptibility of the bacteria in a first group of theplurality of fluid containers and the second light source for measuringthe susceptibility of the bacteria in a second group of the plurality offluid containers.
 33. The optical measuring instrument of claim 32,wherein the first group of the fluid containers are located in thecuvette on a first locus having a first radius, and the second group ofthe fluid containers are located in the cuvette on a second locus havinga second radius, the first radius being different from the secondradius.
 34. The optical measuring instrument of claim 27, wherein thecuvette includes a top cover being initially removed from a main body ofthe cuvette to permit the filling of the fluid containers with theplurality of fluid samples, the top cover being attachable to the mainbody after fluid containers are filled.
 35. The optical measuringinstrument of claim 27, wherein the at least one antimicrobial agent iseither an antibiotic or a drug.
 36. The optical measuring instrument ofclaim 27, wherein at least some of the fluid containers contain the atleast one antimicrobial agent at different concentrations.
 37. Theoptical measuring instrument of claim 27, wherein the at least oneantimicrobial agent is one of a plurality of different antimicrobialagents, and wherein at least some of the individual fluid containersinclude at least some of the different antimicrobial agents.
 38. Amethod of anti-microbial testing, comprising: placing each of aplurality of the fluid samples having a bacteria concentration and atleast one anti-microbial agent in a corresponding one of a plurality offluid chambers located within a cuvette, the fluid chambers each havingan input window and an output window; registering the cuvette on arotatable platform associated with an optical measuring instrument;incrementally rotating the rotatable platform so as to sequentiallytransmit an input beam into the input windows of the fluid containers,wherein the input window and the output window are vertically arrangedwith the fluid sample located therebetween; and in response to passingthe input beam through each of the fluid samples, measuring a firstforward-scatter signal for each of the fluid containers over a period oftime to determine the susceptibility of the bacteria in the fluid sampleto the corresponding anti-microbial agent within the fluid container.39. The method of claim 38, further including: incubating the fluidsamples in the optical measuring instrument before and after measuringthe first forward-scatter signal; and after a period of time,sequentially passing the input beam through each of the fluid containersand measuring a second forward-scatter signal for each of the fluidcontainers, a difference between the first forward-scatter signal andthe second forward-scatter signal being indicative of a change in theconcentration of bacteria.
 40. The method of claim 39, furthercomprising determining that at least one fluid sample includes a certainconcentration of bacteria in response to the difference between thefirst forward-scatter signal and the second forward-scatter signal. 41.The method of claim 38, wherein at least some of the plurality of fluidcontainers include the at least one anti-microbial agent at differentconcentrations, the plurality of fluid samples being derived from thesame fluid sample source, the method further includes determining theeffects of the at least one anti-microbial agent based, in part, on themeasuring of the first forward-scatter signal.
 42. The method of claim38, wherein the at least one antimicrobial agent is one of a drug or anantibiotic.